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Comorbidity of hypertension and hepatobiliary pathology has negative medical and social consequences, including an increase in the indicators of hospital admissions, disability and mortality., Objective: The aim was to study the occurrence of hypertension combined with hepatobiliary diseases depending on social status, gender and age in 2003-2017 and their influence on indicators of metabolic processes in patients with a therapeutic profile., Methods: A cross-sectional study using the inpatients' medical record database of the clinic of Federal Research Centre for Basic and Translational Medicine (Novosibirsk, Russia), which collects demographics, diagnoses (using ICD-10 codes), procedures and examinations of all inpatients from 2003-2017 was conducted. The incidence of comorbidity of hypertension and hepatobiliary pathology depending on age, gender and social status, based on the analysis of 13496 medical records was examined. A comparative analysis of biochemical parameters characterizing the main types of metabolism (lipid, protein, carbohydrate and purine) was carried out in 3 groups of patients: with hypertension; with hepatobiliary pathology, and with a combined pathology., Results: During the years 2003-2005, there was the greatest frequency of this comorbidity in workers, in women, in the age group 60 years and older. In 2009-2017, the highest incidence was observed in the male administrative staff. In patients with this comorbidity, more pronounced changes in carbohydrate, protein, lipid and purine metabolism were found in comparison with groups of patients with isolated diseases., Conclusion: The results highlight the need to improve the system of prevention and treatment of comorbidity taking into account sex, age, occupation and features of metabolism., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Laboratory evaluation of the hepatobiliary system has an important role in the diagnosis, monitoring, and assessment of patients with hepatobiliary diseases. Serum liver enzyme activities can be divided into markers of hepatocellular injury and cholestasis. Liver function can be assessed in several ways, including assessment of synthetic capacity, measurement of ammonia, and measurement of bile acids. It is essential to have an understanding of the performance characteristics and limitations of these tests in order to use them appropriately. This article reviews the laboratory parameters commonly used to aid diagnosing hepatobiliary disorders in dogs and cats., (Published by Elsevier Inc.)

The liver plays a crucial role in all aspects of coagulation because most factors that regulate procoagulation, anticoagulation, and fibrinolysis are produced, cleared, and/or activated in the liver. Establishing the coagulation status of an individual patient with hepatobiliary disease can therefore be challenging. Although, classically, patients with hepatobiliary disease were thought of as potentially hypocoagulable, hypercoagulability also occurs. The article summarizes the breadth of coagulation abnormalities that have been reported in dogs and cats with hepatobiliary disease and provides strategies to respond to bleeding and thrombotic risk., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Routine biochemical tests generally include serum enzymes, proteins, and other markers useful for identifying hepatobiliary disease in dogs and cats. Obtaining results outside the reference intervals can occur with direct hepatocellular injury, enzyme induction by hepatocytes or biliary epithelium, or decreased hepatic function. However, detection of biochemical abnormalities does not necessarily indicate clinically significant disease. For a comprehensive approach to detection and treatment of hepatobiliary disease, the laboratory results must be correlated with the history and physical examination findings, diagnostic imaging results, and other assays., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: To evaluate the efficiency and safety of using statins in combination with ursodeoxycholic acid (UDCA) in patients with this or another liver disease at high risk for cardiovascular events (CVE)., Subjects and Methods: A register of 262 patients at high risk for CCE who needed statin therapy and have concomitant chronic liver and biliary tract diseases was created in 5 cities of the Russian Federation., Results: After addition of statins or adjustment of their doses, the patients were recommended to include UDCA into their therapy. Six months after stabilization of the dose of statins, the whole group showed a significant reduction in the levels of total cholesterol and low-density lipoprotein (LDL) cholesterol. Assessment of the laboratory parameters responsible for the safety of statin intake revealed no deterioration in the trend in the activity of alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, lactate dehydrogenase, as well as an increase in the serum level of bilirubin. The data obtained using a special questionnaire indicated that 196 patients had taken UDCA and 56 had not. The UDCA and non-UDCA subgroups did not differ in age, weight, or baseline lipid metabolic disturbances. An additional analysis showed that by the end of 6 months, the goal levels of LDL cholesterol in the UDCA and non-UDCA groups were reached in 37 and 20%, respectively (p = 0.01)., Conclusion: UDCA added to statin therapy in patients at high risk for CVE and concurrent liver diseases contributes to an additional reduction in total cholesterol and LDL cholesterol and prevents enhanced hepatic transaminase activities.

Objective: To determine signalments, clinical features, clinicopathologic variables, imaging findings, treatments, and survival time of cats with presumed primary copper-associated hepatopathy (PCH) and to determine quantitative measures and histologic characteristics of the accumulation and distribution of copper in liver samples of cats with presumed PCH, extrahepatic bile duct obstruction, chronic nonsuppurative cholangitis-cholangiohepatitis, and miscellaneous other hepatobiliary disorders and liver samples of cats without hepatobiliary disease., Design: Retrospective cross-sectional study., Animals: 100 cats with hepatobiliary disease (PCH [n = 11], extrahepatic bile duct obstruction [14], cholangitis-cholangiohepatitis [37], and miscellaneous hepatobiliary disorders [38]) and 14 cats without hepatobiliary disease., Procedures: From 1980 to 2013, cats with and without hepatobiliary disease confirmed by liver biopsy and measurement of hepatic copper concentrations were identified. Clinical, clinicopathologic, and imaging data were compared between cats with and without PCH., Results: Cats with PCH were typically young (median age, 2.0 years); clinicopathologic and imaging characteristics were similar to those of cats with other liver disorders. Copper-specific staining patterns and quantification of copper in liver samples confirmed PCH (on the basis of detection of > 700 μg/g of liver sample dry weight). Six cats with PCH underwent successful treatment with chelation (penicillamine; n = 5), antioxidants (5), low doses of elemental zinc (2), and feeding of hepatic support or high-protein, low-carbohydrate diets, and other hepatic support treatments. One cat that received penicillamine developed hemolytic anemia, which resolved after discontinuation of administration. Three cats with high hepatic copper concentrations developed hepatocellular neoplasia., Conclusions and Clinical Relevance: Results suggested that copper accumulates in livers of cats as primary and secondary processes. Long-term management of cats with PCH was possible.

Paired serum bile acid (SBA) samples from 30 dogs with presumptive hepatobiliary disease and 30 apparently healthy dogs were submitted to three diagnostic laboratories to validate agreement between these facilities. Sensitivities and specificities ranged from 50% to 70% and from 74% to 85%, respectively, for all laboratories. The κ index confirmed almost perfect agreement between laboratories. Variation in sample handling and processing by different laboratories should not be considered a primary factor when aberrant SBA values are encountered. Documenting agreement between laboratories is essential as inconsistencies could direct unnecessary medical or surgical intervention when patients are evaluated at different hospitals during the course of their disease.

The purposes of this retrospective study were to assess the prevalence of gallbladder sludge (GBS) in a population of cats presented for abdominal ultrasound in a teaching hospital and to determine its association with increased serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (TB). Gallbladder sludge was detected in 152 (14%) of the cats undergoing abdominal ultrasound between 2004 and 2008. This population was compared to a control group of 32 cats without GBS. Alanine aminotransferase, ALP, and TB mean values were significantly higher in cats with GBS than in controls (P ≤ 0.0005) and odds for increased values in cats with GBS were 4.2 [95% confidence interval (CI): 1.6 to 11.0], 9.5 (95% CI: 2.2 to 41.7), and 4.1 (95% CI: 1.5 to 11.5), respectively (P ≤ 0.007). In conclusion, GBS is an uncommon ultrasonographic finding in cats that is predictive of increased liver enzymes and TB. More studies are needed to establish potential links between GBS and hepatobiliary disease in cats.

Objective: To determine: (1) changes in blood ammonia, bile acid (BA), bilirubin, triglyceride, and glucose concentrations and liver enzyme activities in perioperative colic patients and (2) the association between these laboratory findings and short-term survival., Design: Prospective observational clinical study., Animals: Thirty-two adult horses undergoing exploratory celiotomy for colic., Interventions: None., Measurements and Main Results: Blood samples were collected preoperatively and at 24-36 and 72-84 hours postoperatively and analyzed for blood ammonia, BA, bilirubin, triglyceride, and glucose concentrations and sorbitol dehydrogenase (SDH) and gamma glutamyl transferase (GGT) activities. Short-term survival was defined as survival to hospital discharge. Data were analyzed using a Fisher's exact test and analysis of variance. Mildly increased blood ammonia concentrations were present in 2 horses at admission. Postoperative blood ammonia concentrations were within reference intervals in all horses. There were increases in liver enzyme activities as well as in BA, triglyceride, and total bilirubin concentrations. Horses with markedly increased admission BA concentrations and SDH activities did not survive. BA concentrations and SDH activities decreased postoperatively. There was no association between GGT activity and survival; GGT activity remained increased postoperatively. Blood triglyceride concentration was increased in almost all horses postoperatively; horses that did not survive had higher triglyceride concentrations at 24-36 hours postoperatively than horses that survived., Conclusion: Alterations in metabolism and hepatobiliary function are common in colic patients. The results of this study provide further prognostic indices for colic patients and highlight areas for improvement in patient management., (© Veterinary Emergency and Critical Care Society 2010.)

Objective: To determine the diagnostic value of protein C (PC) for detecting hepatobiliary disease and portosystemic shunting (PSS) in dogs., Design: Prospective study., Animals: 238 clinically ill dogs with (n = 207) and without (31) hepatobiliary disease, including 105 with and 102 without PSS., Procedures: Enrollment required routine hematologic, serum biochemical, and urine tests; measurement of PC activity; and a definitive diagnosis. Total serum bile acids (TSBA) concentration and coagulation status, including antithrombin activity, were determined in most dogs. Dogs were grouped into hepatobiliary and PSS categories. Specificity and sensitivity were calculated by use of a PC cutoff value of 70% activity., Results: Specificity for PC activity and TSBA concentrations was similar (76% and 78%, respectively). Best overall sensitivity was detected with TSBA, but PC activity had high sensitivity for detecting PSS and hepatic failure. Protein C activity in microvascular dysplasia (MVD; PC > or = 70% in 95% of dogs) helped differentiate MVD from portosystemic vascular anomalies (PSVA; PC < 70% in 88% of dogs). A receiver operating characteristic curve (PSVA vs MVD) validated a useful cutoff value of < 70% activity for PC., Conclusions and Clinical Relevance: Combining PC with routine tests improved recognition of PSS, hepatic failure, and severe hepatobiliary disease and signified a grave prognosis when coupled with hyperbilirubinemia and low antithrombin activity in hepatic failure. Protein C activity can help prioritize tests used to distinguish PSVA from MVD and sensitively reflects improved hepatic-portal perfusion after PSVA ligation.

Objective: The aim of this study is to determine the etiologies of serum gamma glutamyltransferase (GGT) elevation and relations between multiple etiologies prevalent in the Pursaklar region of Ankara in Turkey., Patients and Methods: The patients referred to the Family Medicine and Internal Medicine departments with various complaints from the Pursaklar region of Ankara between July 2000 and July 2002 were evaluated, and values for GGT, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) levels were determined. GGT elevation was classified as being associated with hepatic, biliary, and other origins., Results: For GGT elevation, hepatobiliary etiologies were more prevalent. The most prevalent hepatic etiology was nonalcoholic steatohepatitis, followed by biliary etiologies. The most prevalent etiology of biliary origin was cholelithiasis. Other etiologies, in order of prevalence, were drug exposure and urinary infection. There were no gender-related differences for distribution of GGT elevation; however, the GGT values for women were higher than those for men.

Background/aims: Levels of S-PIIINP (serum aminoterminal propeptide of type III procollagen) have been shown to be increased in patients with primary sclerosing cholangitis and inflammatory bowel disease. The aim of the study was to investigate the serum concentrations of PIIINP and laminin in inflammatory bowel disease patients, their relationship with inflammatory bowel disease-associated hepatobiliary and pancreatic dysfunction, and to correlate them with clinical, endoscopic, and histologic variables., Methodology: S-PIIINP and S-laminin were measured in 222 consecutive inflammatory bowel disease patients, who were screened for abnormal liver and pancreatic enzymes and for pancreatic exocrine hypofunction with the p-aminobenzoic acid test (215 patients). The patients with abnormal screening results were further scheduled for endoscopic retrograde cholangiopancreatography, liver biopsy, secretin test and ultrasound., Results: S-PIIINP and S-laminin were abnormally high in 19% and 40% of all inflammatory bowel disease patients, respectively. The elevated levels of the fibrosis markers were associated with laboratory signs of either hepatobiliary or pancreatic disease. Hepatobiliary disease was found in 37 (17%) of inflammatory bowel disease patients, 15 of whom had primary sclerosing cholangitis. The median levels of S-PIIINP and S-laminin were significantly higher in patients with hepatobiliary disease than in those without (P < 0.0001 and P < 0.001, respectively), being most strikingly elevated in primary sclerosing cholangitis. Abnormal pancreatic screening tests were found in 67 (30%) patients. High levels of S-PIIINP and S-laminin were also significantly associated with low values in p-aminobenzoic acid (P < 0.001 and P < 0.005) and secretin (P < 0.01 and P < 0.05) tests, but not with inflammatory bowel disease category, endoscopic or histological disease extent, frequency of bowel resection or actual clinical activity., Conclusions: In inflammatory bowel disease, increased S-PIIINP and S-laminin are associated with hepatobiliary and pancreatic disorders.

Background: Alkaline phosphatase (ALP) is an important enzyme mainly derived from the liver, bones and in lesser amounts from intestines, placenta, kidneys and leukocytes. An increase in ALP levels in the serum is frequently associated with a variety of diseases. This study was done in order to determine the diseases associated with a high ALP level among Thai adult hospitalized patients., Method: A review was made of medical records of inpatients with high ALP level above 1000 IU/L in King Chulalongkorn Memorial Hospital, Thailand from January 1999 to December 1999. Excluded were cases of (a) patients who have bone involvements with malignancies, (b) pediatric patients younger than 15 years old and c) HIV-seropositive patients., Results: A total of 181 hospitalized patients with eligible medical records were identified (96 males and 85 females, mean age 49.4 +/- 16.1 years). Their ALP levels ranging from 1,001 to 3,067 IU/L, these patients were divided into four groups., Conclusion: High serum ALP levels in hospitalized patients were commonly found in three major groups having obstructive biliary diseases, infiltrative liver disease and sepsis. The study results were in accordance with previous reports in developed countries. Nonetheless, cholangiocarcionoma and some tropical diseases unique to our setting were also detected in these cases, where there was a marked elevation of serum ALP.

Background/aims: In this study, we examined the influence of clinical treatments in the perioperative period upon PIVKA-II (plasma levels of protein induced by vitamin K absence or antagonist-II) in patients with hepatocellular carcinoma and pancreatobiliary diseases., Methodology: During a perioperative period, plasma PIVKA-II levels were measured in 144 patients with various hepatobiliary and pancreatic diseases by two types of EIA kit, using the conventional monoclonal antibody MU-3 and the new monoclonal antibody 19B7; Thrombotests were given at the same time., Results: PIVKA-II of hepatocellular carcinoma patients showed higher reactivity with MU-3 than with 19B7. On the other hand, PIVKA-II of pancreatobiliary malignancies showed higher reactivity to 19B7 than it did to MU-3. In hepatocellular carcinoma patients, there was no correlation between PIVKA-II and Thrombotest levels; however, a significant correlation was found in patients with obstructive jaundice due to pancreatobiliary cancer. PIVKA-II levels decreased gradually to normal range within about 2 weeks after the curative operation. PIVKA-II levels in the patients receiving antibiotics containing N-methyl-thiotetrazole without administration of vitamin K remained high as long as the antibiotics were administered, but decreased to normal range as soon as the administration was finished., Conclusions: PIVKA-II which is produced by hepatocellular carcinoma may be different from that produced by obstructive jaundice due to pancreatobiliary malignancies. The clinical treatments in perioperative period, such as the administration of antibiotics containing N-methyl-thiotetrazole or vitamin K, readily influence PIVKA-II levels. Therefore, abnormal PIVKA-II levels must be carefully interpreted in the diagnosis of hepatocellular carcinoma and pancreatobiliary malignancies.

The level of lipid peroxidation (LPO) products increases in the blood of patients with chronic diseases of the liver and acute cholecystitis with mechanical jaundice. The values normalize after surgery for acute cholecystitis, whereas therapy for chronic diseases of the liver virtually does not correct them. These data demonstrate the relationship between intensity of free-radical oxidation and severity of hepatobiliary process and between plasma content of LPO products and level of serum bilirubin.

Nitric oxide (.NO) is known to influence circulatory, neural, immunologic, and metabolic alterations. To evaluate the clinical significance of .NO production under surgical stress, serial measurements of plasma nitrite plus nitrate levels were performed in 45 surgical patients. Group A included 19 patients who underwent major surgery with uneventful postoperative courses. Group B included 18 patients who underwent laparoscopic cholecystectomy. Group C included 8 patients whose surgery was complicated by intra-abdominal abscesses. Eight healthy volunteers served as controls. Plasma nitrate levels were determined with a redox chemiluminescence .NO analyzer and coincided with measurements made by high-performance liquid chromatography (r = 0.868, p < 0.0001, 58 samples). During laparotomy, arterial nitrate levels correlated well with peripheral, portal, and hepatic venous nitrate levels (r = 0.966, 0.938, and 0.949, respectively; p < 0.0001). A significant decrease in nitrate from preoperative levels in groups A (postoperative day (POD) 1 and 3; p < 0.0005) and B (POD 1, p < 0.0001) was observed; nitrate levels in group C did not decrease for 14 days after surgery. Plasma nitrate levels in groups A and B were significantly different (POD 1 through 6, p < 0.05) and at POD 3 were significantly lower in group A (p < 0.005). Plasma nitrate levels measured before and after fasting or food intake were not significantly different. These results suggest that surgical stress leads to a decrease in the end product of .NO in the whole body, and that the greater the surgical stress the longer the duration of decreased .NO production.

Serum bile acid concentrations were measured after food had been withheld for 12 hours (fasting serum bile acid [FSBA] concentration) and 2 hours after a meal (post-prandial serum bile acid [PSBA] concentration) using a direct enzymatic procedure in 108 cats clinically suspected of having hepatobiliary disease. In all cats, liver tissue was examined histologically to confirm the diagnosis. Twenty-six cats did not have histologic evidence of hepatobiliary disease and served as controls. The remaining 82 cats had hepatobiliary disease including hepatic lipidosis (n = 20), portosystemic vascular anomaly (n = 24), hepatic necrosis (n =13), hepatic neoplasia (n = 8), or cholestatic hepatic disease(n = 17). Sensitivity and specificity of measuring FSBA and PSBA concentrations were calculated for each test alone and when results were interpreted in combination (ie, in series and in parallel), and were compared with sensitivity and specificity of routinely used serum biochemical tests, including measuring serum activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase, and measuring serum concentrations of cholesterol, BUN, and total bilirubin. When tests were considered individually, determination of FSBA and PSBA concentrations had higher specificity than did the other tests (using a cutoff of 15 mumol/L for FSBA concentration and of 20 mumol/L for PSBA concentration). Determination of PSBA concentration had the highest sensitivity of all single tests in cats with hepatic lipidosis, portosystemic vascular anomaly, or cholestasis; determination of alanine aminotransferase activity or PSBA concentration had the highest sensitivity for cats with hepatic necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Using an electrophoretic technique on cellulose acetate, three multiple forms of the 5'-nucleotidase (5'NU) with mobilities alpha 1, alpha 2, and beta appear in the serum of healthy subjects. The difference between the alpha 1 and alpha 2 isoforms lies in their sialylation degree, the alpha 2-5'NU being a de-sialylated form. In 147 patients with different hepatobiliary diseases the alpha 2 isoform was present in only 19% of cases, and there was no significant difference in the activity of total 5'NU, alpha 1-5'NU and beta-5'NU between patients with or without alpha 2-5'NU, alpha 1-5'NU and beta-5'NU (P < 0.001), as with other biochemical indicators of liver damage. It is suggested that in hepatobiliary diseases an increase of the sialylation of serum 5'NU occurs, which would explain the absence of the desialylated alpha 2 isoform in the majority of cases. However, the decrease of hepatic receptors of asialoglycoproteins would lead to an increase of this de-sialylated isoform in the serum of certain patients.

A reversed phase high performance liquid chromatographic method for the high sensitivity determination of individual bile acids in serum using a C18 column with a ternary solvent system combined with fluorometric techniques using immobilized enzymes is described. A computer-assisted diagnosis system using pattern recognition was developed to assist the clinical diagnosis of various liver and biliary diseases. A total consistency rate of 95% can be reached using this system.

Objective: The purpose of the present study was to demonstrate the use of logistic regression models in the prediction of diseases using the prediction of canine primary and secondary hepatobiliary diseases as an example. Briefly, in a logistic regression model independent variables (i.e. the analytical results) are combined in a linear equation that is used to estimate the logarithm of the odds (logit) of an event (i.e. having primary or secondary hepatobiliary disease). From the estimated logit given by the logistic regression model, a conditional probability of the event (i.e. having primary or secondary hepatobiliary disease) can be calculated., Study Design: Twenty-six dogs with verified primary and secondary hepatobiliary diseases and 19 dogs, initially suspected to have hepatobiliary diseases, but with apparently other diseases, were included in the study. The following clinical chemical parameters were measured: alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (AP), bilirubin(Total) (TB), urea, glucose, retention of bromosulphthalein (BSP), fasting and postprandial total serum bile acid concentration (FSBA and PSBA). Logistic regression analysis, using the CATMOD procedure in SAS, was used to select which of the measured parameters should be included in the model, and to derive a logistic regression model using the selected parameters. To observe more closely the potential of the logistic regression model, the model was also used to classify a test group consisting of 13 dogs (6 dogs with hepatobiliary diseases and 7 dogs with other diseases)., Results: By logistic regression analysis, ASAT and PSBA were selected to be included in the final model, and the final logistic regression model was Y = -3.194 + 0.044.PSBA + 3.251.ASAT. The logistic regression model classified correctly 38 (84%) of 45 dogs in the present study. Specifically, 21 (81%) of 26 dogs with verified primary or secondary hepatobiliary diseases and 17 (90%) of 19 dogs with various other diseases were correctly classified by the logistic regression model. When the model was used on the test group, 5 (83%) of 6 dogs with hepatobiliary diseases and 7 dogs (100%) of 7 dogs with other diseases were correctly classified., Conclusions: Even though the logistic regression model derived in the present study only serves as an example, thus reducing the practical usefulness of the derived logistic regression model, the present study indicates a great potential of logistic models for the diagnosis of diseases.

We have investigated the correlation between the arterial blood ketone body ratio (AKBR) and beta-hydroxybutyric acid (HBAC) in the course of a 75 g glucose tolerance test. The correlation was revealed to be represented by an equation of Y = A + BX [X = log(HBAC), Y = log(AKBR)] with high significance. This expression existed in both normal individuals and patients with liver, biliary tract or pancreas disease. The postoperative course was unsatisfactory because of liver dysfunction in cases whose value B was more than -0.6 in bisegmentectomy and more than -0.45 in uni- or subsegmentectomy. The coefficient B in the equation was suggested to contribute to the evaluation of hepatic functional reserve.

The fasting and 2 h postprandial total serum bile acid concentrations (FSBA and PSBA), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin (Total), and retention of bromosulphthalein were determined in a group of dogs with various hepatobiliary disorders as well as in a group of dogs with other diseases than hepatobiliary disorders. Although FSBA and PSBA were generally elevated in cases of hepatobiliary disorders, no distinction between different disease groups could be made based solely on FSBA and PSBA. FSBA and PSBA were found to be relatively sensitive and specific parameters compared to the other hepatic tests. PSBA tended to be superior to the other parameters investigated in terms of sensitivity, specificity, positive predictive value, and negative predictive value.

A study was carried out on the clinical significance of changes in the serum level of mitochondrial aspartate aminotransferase before and after surgery on patients suffering from various hepato-biliary diseases. The patients included those whose livers were impaired with cirrhosis, jaundice, or direct surgical intervention such as hepatectomy. It was found that the postoperative liver function of patients whose preoperative values of serum mitochondrial aspartate aminotransferase had been less than 10 Karmen units recovered with a favorable course, whereas that of patients whose values had exceeded 20 units deteriorated with persistent jaundice, ascites or hepatic insufficiency. Both the sensitivity and specificity of respective liver function tests were examined by the preoperative values of routine liver function tests and the postoperative liver functions. The results revealed the serum value of mitochondrial aspartate aminotransferase to be more sensitive than the other tests, while specificity was not significantly different. A safety limit for a favorable postoperative course in terms of liver function was observed in patients showing a preoperative serum mitochondrial aspartate aminotransferase activity of below 10 units. Thus, serum mitochondrial aspartate aminotransferase activity could be applied as a useful marker for hepato-biliary surgery.

Blood and bile porphyrin concentrations were measured in cattle with protoporphyria and compared with those in human beings with the disease. Whereas the mean RBC porphyrin concentration in cattle was 18-fold greater than in human beings, the mean bile porphyrin concentration was only 78% greater. Sequential measurements over a 30-hour period in 1 animal with a bile fistula indicated that the ratio of total porphyrin to total bile acid in bile varied minimally. When the animal was given an IV infusion of taurocholate, the biliary excretion rate of porphyrin increased in parallel with that of bile acid, because of enhancement of bile flow. Thus, in cattle with protophorphyria, the concentration of porphyrin in bile is low compared with that of porphyrin in RBC, in contrast with findings in human beings, and adequate amounts of bile acids are secreted to maintain efficient protoporphyrin excretion. This explains, in part, why hepatobiliary disease has not been observed in cattle with protoporphyria, but has been seen in human beings with the disease.

Serum Bilirubin was fractionated by newly developed reversed phase high performance liquid chromatography (HPLC) into 5 fractions: delta (delta-Bilirubin, B delta), gamma (bilirubin diglucuronide, BDG), beta (Bilirubin monoglucuronide, BMG), beta' ((Z, E,)- and/or (E, Z)-bilirubin IX alpha) and alpha ((Z, Z)-bilirubin IX alpha). Sera of healthy subjects and of patients with unconjugated hyperbilirubinemia showed predominantly alpha fraction with a small amount of beta' fraction. Trace amounts of delta fraction were detected in a few cases. The results of fractionation of serum bilirubin in 159 patients with various hepatobiliary diseases suggested that the ratios B delta/(B delta + BDG + BMG) and BMG/B delta can be useful parameters to follow patients with jaundice, compared with the reported B delta/total bilirubin which did not always reflect the jaundice stage, especially in cases with low serum bilirubin levels.

Both serum cholylglycine (CG) and sulfolithocholylglycine (SLCG) levels were radioimmunoassayed by PEG method in 209 samples (204 hepatobiliary diseases, 5 normal controls). 1) The results revealed that serum bile acid levels were excellent indicators for hepatic dysfunction in comparison with the conventional liver function tests. 2) Means of 19.4 +/- 9.3 microgram/dl for CG and 21.7 +/- 6.7 microgram/dl for SLCG were obtained in controls. Most hepatobiliary diseases demonstrated abnormally high bile acid levels, with extremely high CG values in conditions with bile stasis. 3) To differentiate various hepatobiliary diseases more clearly, the ratio of the primary and secondary bile acids (CG/SLCG ratio) was introduced (1.0 +/- 0.6 for controls). In cases of bile stasis, CG/SLCG ratios ranged from 7.8 +/- 4.8 for intrahepatic cholestasis to 34.8 +/- 27.6 for congenital biliary atresia, while other hepatic disorders demonstrated relatively low values. We conclude that the CG/SLCG ratio is a useful index for cholestasis. Diagnosis of the congenital biliary atresia could be possible.

In 131 patients on a medical service and 97 patients on a surgical service, in whom a diagnosis of hepatobiliary disease was verified in the hospital, the diagnostic value of routine liver tests performed soon after admission was evaluated by stepwise discriminant analysis. By measurements of alanine aminotransferase, alkaline phosphatases, gamma globulin, prothrombin time, bilirubin, and albumin, half of the medical patients were correctly classified into one of seven diagnostic categories. Aminotransferase contributed most to the classification, being twice as effective as random allocation. Decreasing the number of diagnostic categories to three (hepatitis, fatty liver, and chronic liver disease) increased the frequency of correct allocation to 80%. The allocation of all the patients to seven medical and four surgical diagnostic categories by means of four tests (aminotransferase, alkaline phosphatases, prothrombin time, and bilirubin) was significantly improved by each step with a misclassification rate of 55% when all tests were used. A reduction of the diagnostic groups to five (hepatitis, fatty liver, chronic liver disease, duct obstruction and tumor) increased the frequency of correct allocation to 63%. The analysis demonstrates the limited diagnostic effectiveness of routine liver tests when used alone. The absolute discrimination values depend on the a priori frequencies of the diagnostic groups investigated, and therefore may vary from time to time and from place to place.

Fasting and postprandial concentrations in serum of 3 alpha-hydroxy-bile acids and gamma-glutamyl transferase were measured in 138 consecutive patients, 62 with (D) and 76 without (D) hepatobiliary disease. The maximum efficiencies of the three tests--that is, the fractions of patients allocated correctly to the D or D group at the optimum discrimination values--were 0.85, 0.84, and 0.83, respectively. Furthermore, the predictive values and nosographic sensitivities and specificities were rather similar. When the three tests were combined, the nosographic sensitivity increased significantly to a value of 0.84, and the corresponding specificity was 0.91. The diagnostic value of the absolute postprandial increase in serum bile acid concentration was slightly inferior to the diagnostic values of the fasting and postprandial serum bile acid concentrations and, finally, the relative postprandial serum bile acid increase was of no diagnostic value at all.

In 104 patients with acute virus hepatitis, chronic hepatitides, cirrhoses, fatty livers and biliary diseases with partial and complete obstructive jaundice, respectively, IgG, IgA, IgD, beta1A- and beta1E-globulin, cholinesterase, total protein, and albumin, in 45 of these patients additionally prealbumin, retinol binding protein, thymol turbidity test were determined as well as an electrophoretic separation of the serum was performed. 11 persons with healthy liver served as control group. According to the results of univariate and multivariate variance analyses with following test of redundance (test for indispensability) and analysis of discriminance with calculations of reclassification IgD, beta1E-globulin and retinol binding protein were identified as not evident or redundant. Electrophoresis and thymol turbidity test give sufficient basis informations and can further be recommended for orienting examinations. Immune globulinogrammes from IgB, IgA and IgM are suitable as so-called mesenchyma tests particularly for controls of the course. Prealbumin and cholinesterase prove to be the most sensitive parameter of synthesis, whereas albumin and beta1A-globulin possess a high prognostic evidence.

Serum prealbumin concentrations have been studied, by a quantitative immunological procedure, in patients with secondary carcinoma of the liver, chronic active hepatitis, alcoholic hepatitis, cryptogenic cirrhosis, obstructive jaundice, inflammatory bowel disease, and myocardial infarction. The results showed that prealbumin concentration is significantly decreased when liver function is impaired. In diseases not associated with liver damage the concentrations of prealbumin were within the normal range. The advantage of this biochemical procedure is that serum prealbumin concentration is a true index of liver function, whereas serum enzyme activities signify only the degree of hepatocellular damage, which may not always quantitatively reflect liver function. Determination of serum prealbumin is therefore valuable in the diagnosis of liver disease and in the monitoring of treatment.

Quantitative determination of the abnormal plasma lipoprotein of cholestasis LP-X has been performed in 81 LP-X positive patients with different liver disorders. Great variations in the plasma concentration of LP-X were demonstrated both in the 45 patients with intrahepatic cholestasis (acute hepatitis, toxic hepatitis, primary biliary cirrhosis and cholangitis) and in the 36 patients with extrahepatic cholestasis (extrahepatic biliary obstruction by tumours and choledocholithiasis). The plasma concentratkons of LP-X in the patients with extrahepatic cholestasis (median 158 mg/100 ml) were significantly (psmaller than 0.001) higher than in the patients with intraphepatic cholestasis (median 25 mg/100 ml) was exceeded by 42% of the patients with extrahepatic biliary obstruction, and 33% of the patients with extrahepatic biliary obstruction, had LP-X LEVELS ABOVE 400 MG/100ML. The plasma concentration of LP-X was significantly correlated to the plasma activity of alkaline phosphatases and serum bilirubin, but seemed to be superior to these two parameters in the differentiation between intrahepatic and extrahepatic cholestasis. Plasma levels of LP-X above 400 mg/100 ml are highly indicative of extrahepatic biliary obstruction.

Fasting concentrations of S-cholate, S-chenodeoxycholate, S-aminotransferases, S-bilirubin, S-alkaline phosphatases, and S-glutamyltransferase were determined in 564 outpatients with disorders of the liver and gastrointestinal tract. Unsulphated conjugates of cholic (fS-C) and chenodeoxycholic acid (fS-CDC) were determined by radioimmunoassay. In patients with increased serum bile acid concentrations fS-C and fS-CDC were linearly correlated, and the fS-C/fS-CDC ratio was similar in all patient groups. The incidence of false-positive results of fS-CDC was probably due to inadequate fasting and comparison of fS-C only with the liver tests. In 51 patients with verified cirrhosis fS-C was significantly correlated with S-bilirubin in a semilogarithmic relation but not with S-alkaline phosphatases or S-glutamyltransferase. fS-C was found to be a sensitive indicator of liver disease in the anicteric stage. Of 207 patients with inflammatory bowel disease, 63 had 1 or several of the results of liver tests for cholestasis elevated. There was no correlation between the different tests. In these patients and all patients with gastrointestinal disorders the commonest single finding was an elevation of S-alkaline phosphatases not associated with cholestasis.

The prevalence of low serum urea nitrogen concentrations (less than 50 mg/L) in our patient population was 1.2% (151 per 12,380 determinations), representing 95 individual cases. Of these, 81 of the patients' charts were located, reviewed, and classified into two groups, those with and those without hepatobiliary disease. Hepatobiliary disease was found in 36% of the 81 patients; 90% of these showed evidence of alcohol abuse, as did 19% of those without hepatobiliary disease. The remaining patients without hepatobiliary disease had various clinical conditions: psychiatric disorders (14.8%), overhydration (12.3%), endocrine disorders (7.4%), cardiovascular diseases (4.9%), prednisone administration (3.7%), and special diets (2.5%). Thus, in our patient population the most frequent cause of low serum urea nitrogen concentrations was alcohol abuse, found in about half of the cases.

Individual non-sulfated bile acids in the serum of 65 patients with hepatobiliary diseases were quantitated by mass fragmentography. Serum with deuterium labeled deoxycholic acid as an internal standard was hydrolyzed with strong alkali, extracted with ether after acidification under cooling, and quantitated by mass fragmentography as the hexafluoroisopropyl-trifluoracetyl derivatives. In obstructive jaundice, the ratio of cholic to chenodeoxycholic acid was significantly higher than others. Cholic or chenodeoxycholic acid levels were correlated with total bilirubin levels in obstructive jaundice and acute hepatitis. Lithocholic acid value was independent of the degree of liver injury. Total bile acid value was helpful in estimating the extent of liver cell injury and cholestasis, and these two pathological conditions can be distinguished to some extent by cholic to chenodeoxychoic acid ratio.

Serum 25-hydroxy-vitamin D (25-OHD) concentrations were measured in 49 patients with hepatobiliary disease in infancy. Low mean values were found in groups of patients with biliary atresia, neonatal hepatitis, choledochal cyst, and chronic intrahepatic cholestatic syndrome. In the group of patients with surgically repaired biliary atresia, the mean value did not differ from normal. Parenteral vitamin D increased 25-OHD in serum in patients with biliary atresia, but did not do so in one patient with neonatal hepatitis. In contrast, oral vitamin D did not increase serum 25-OHD concentrations in patients with biliary atresia. It is concluded that the reduction of serum 25-OHD seen in biliary atresia was largely due to the malabsorption of vitamin D, while in neonatal hepatitis it was due to impairment of 25-hydroxylation of the vitamin.

Repetitive (5 days) ultraviolet treatment was used to improve vitamin D status of 26 pediatric patients suffering from different hepatobiliary disorders. The treatment resulted in a significant improvement of patients' vitamin D and 25-hydroxyvitamin D levels regardless of their disease and other factors such as increased blood bilirubin content or jaundice. Presence of a dependence between the increase in 25-hydroxyvitamin D concentrations after treatment and its original levels was confirmed.